Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1260386 (GSH)
 38,102 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to evaluate postnatal red blood cell (RBC) properties and whole-blood rheology, 36 healthy full-term newborn infants were tested twice (cord blood, 4th-day blood) for whole-blood flow rate, hematocrit, hemoglobin (Hb), RBC count, mean corpuscular volume, mean corpuscular Hb and its concentration, white blood cell and platelet count, plasma fibrinogen, erythrocyte glucose-6-phosphate dehydrogenase, glutathione peroxidase (GSH-Px), glutathione reductase, catalase and superoxide dismutase. Another 38 healthy full-term newborns were tested twice for separation of erythrocytes into fractions of different density. Healthy adults were taken as control. The results showed a decreased whole-blood flow rate in blood drawn on the 4th day with respect to cord blood. A multivariate analysis with flow rate as dependent variable demonstrated a significant positive correlation with GSH-Px on the 4th day. The assays of RBC densities showed a significant increase in the first 4 days.
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PMID:Characteristics and functional properties of red cells during the first days of life. 179 13

Thioltransferase activity was identified and the enzyme purified to apparent homogeneity from human red blood cells. Activity was measured as glutathione-dependent reduction of the prototype substrate hydroxyethyl disulfide; formation of oxidized glutathione (GSSG) was coupled to NADPH oxidation by GSSG reductase (1 unit of activity = 1 mumol/min of NADPH oxidized). The thioltransferase-GSH-GSSG reductase system was shown also to catalyze the regeneration of hemoglobin from the mixed disulfide hemoglobin-S-S-glutathione (HbSSG) and to reactivate the metabolic control enzyme phosphofructokinase (PFK) after oxidation of its sulfhydryl groups. On a relative concentration basis, thioltransferase was about 1200 times more efficient than dithiothreitol in reactivation of phosphofructokinase; e.g., 500 microM DTT was required to effect the same extent of reactivation as that of 0.4 microM TTase. The GSH plus GSSG reductase system without thioltransferase was ineffective for reduction of HbSSG or reactivation of PFK. The average amount of thioltransferase in intact erythrocytes was calculated to be 4.6 units/g of Hb at 25 degrees C. This level of activity is about the same as those of other enzymes that participate in sulfhydryl maintenance in red blood cells, such as GSSG reductase and glucose-6-phosphate dehydrogenase. These results suggest a physiological role for the thioltransferase in erythrocyte sulfhydryl homeostasis. Certain properties of the human erythrocyte thioltransferase resemble those of other mammalian thioltransferase and glutaredoxin enzymes. Thus, the human erythrocyte enzyme, purified about 28,000-fold to apparent homogeneity, is a single polypeptide with a molecular weight of 11,300. Its N-terminus is blocked, it is heat stable, and it contains four cysteine residues per protein molecule. However, the human erythrocyte thioltransferase is a distinct protein based on its amino acid composition. For example, it contains no methionine residues; whereas the related mammalian enzymes described to date have at least one internal methionine residue in their largely homologous sequences.
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PMID:Thioltransferase in human red blood cells: purification and properties. 182 80

Nitrofurantoin is a widely utilized urinary antimicrobial drug which has been associated with pulmonary fibrosis, neuropathy, and hepatitis as well as hemolytic anemia in glucose-6-phosphate dehydrogenase-deficient individuals. Incubation of freshly isolated rat hepatocytes with nitrofurantoin caused oxygen activation as a result of futile redox cycling. Glutathione disulfide (GSSG) was formed and rapidly exported from the cell resulting in complete glutathione (GSH) depletion followed by cell death. However, fructose prevented the export of GSSG from the cell and GSH levels recovered rapidly without cytotoxicity occurring. Fructose did not affect nitrofurantoin metabolism but rapidly depleted cellular ATP levels by approximately 80% which remained depressed during the incubation period. Fructose, however, did not protect hepatocytes from nitrofurantoin-induced cytotoxicity if GSH was depleted beforehand. Protection by fructose only occurred at concentrations which caused ATP depletion. These results suggest that fructose prevents nitrofurantoin-induced toxicity by depleting ATP and thereby preventing the ATP-dependent GSSG efflux. GSSG is retained enabling NADPH and glutathione-reductase to reduce the GSSG back to GSH, thereby protecting the cell from nitrofurantoin-induced oxidative stress.
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PMID:Prevention of nitrofurantoin-induced cytotoxicity in isolated hepatocytes by fructose. 189 74

We have used 1,3-bis(2-chloroethyl)-1-nitrosourea, a selective inhibitor of oxidized glutathione reductase (GSSG-R), to examine the role of this enzyme in regulating the hexose monophosphate shunt (HMS) and to explore how a variety of agents influence glucose decarboxylation in intact human red blood cells (RBCs). Substances tested included primaquine and several other drugs that are specially hemolytic and methemoglobinemic in glucose-6-phosphate dehydrogenase (G6PD) deficiency and related disorders. The results allowed us to distinguish and quantitate contrasting modes of HMS stimulation and to clarify how RBCs respond to different classes of oxidants. Some agents like methylene blue (MB), phenazine methosulfate, and pyrroline carboxylate do not require GSSG-R to increase CO2 production; they activate G6PD and 6-phosphogluconic dehydrogenase by directly oxidizing reduced nicotinamide adenine dinucleotide phosphate (NADPH) to oxidized nicotinamide adenine dinucleotide phosphate (NADP). Other compounds, like ascorbate, nitrofurantoin, and doxorubicin, oxidize GSH primarily; CO2 increases indirectly only when GSSG-R, activated by glutathione disulfide (GSSG), raises the level of NADP. Chemicals like primaquine, daunorubicin, and methylphenylazoformate trigger the HMS by independently oxidizing both NADPH and GSH. Unlike MB, most drugs that are hemolytic in G6PD deficiency activate the HMS in a manner that depends to a variable extent on GSSG-R. This variability may explain hitherto puzzling clinical and pharmacogenetic differences between primaquine and diaminodiphenylsulfone-induced hemolysis.
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PMID:Defenses against oxidation in human erythrocytes: role of glutathione reductase in the activation of glucose decarboxylation by hemolytic drugs. 190 43

Both acute acetaminophen toxicity and physical exercise are accompanied by structural and functional damage to tissues. For acute acetaminophen toxicity, this damage occurs mainly in the liver. This damage, which is believed to be initially caused by oxidation and/or arylation, occurs only after depletion of liver glutathione (GSH). GSH normally protects against oxidation and/or arylation. Prolonged physical exercise also depletes GSH in the body. We hypothesized that with endurance training (repeated oxidant stress) tissues will develop mechanisms to prevent GSH depletion. Our results show that, for the same amount of submaximal exercise, trained rats are able to maintain their levels of GSH or their GSH redox status (in the liver, heart, skeletal muscle and plasma) in contrast to their untrained counterparts. Also, upon administration of acetaminophen, trained rats show a less pronounced depletion in liver GSH than untrained rats. We also hypothesized that training may lead to improved maintenance of tissue GSH homeostasis because of induction in the enzyme pathways of protection. We observe that training significantly increases (50-70%) glutathione peroxidase and reductase, glucose-6-phosphate dehydrogenase, and catalase activity in heart and skeletal muscle. Since GSH, in addition to providing cellular protection, also functions in other physiological processes including transport and metabolism, the training-induced benefits seen here may have more far-reaching consequences than ever before realized.
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PMID:Effects of endurance training and exercise on tissue antioxidative capacity and acetaminophen detoxification. 193 63

In this investigation, glutathione peroxidase (GSH-PX), glutathione reductase (GSSG-RD), glutathione-S-transferase (GSH-S-T), gamma-glutamyl transpeptidase (gamma-GT) and glucose-6-phosphate dehydrogenase (G6PDH) were measured in human hair follicle obtained by plucking as source of keratinized cells. This non-invasive method was used on 27 men and women volunteers ranging from 19 to 102 years. Our results show that GSSG-RD, GSH-S-T, gamma-GT and G6PDH activities decrease as a function of age, whereas GSH-PX activity does not vary. We discriminated 2 groups: a first one from 19 to 60 years with a large dispersion of the enzymatic activities and a second one corresponding to elderly people (up to 70) with a smaller dispersion of the values. This study suggests the keratinocytes possess an age-correlated enzymatic detoxification response potential.
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PMID:Evidence for an age-correlated change in glutathione metabolism enzyme activities in human hair follicle. 196 79

Tissue hypoperfusion leads to cellular oxidative and peroxidative damage due to biochemical disorders in the oxygen and substrate metabolism. The metabolic turnover of glutathione (GSH) represents one the main cytoprotective systems against the peroxide attack and the depletion or defect in resynthesis of this compound is accompanied by pathological consequences. In the present study the clinical effects of glutathione depletion were investigated in conditions of acute tissue hypoxia due to marked haemolysis in glucose-6-phosphate dehydrogenase deficient patients (favism syndrome). In these subjects a significant marker of the tissue oxidative damage was represented by the uric acid blood levels, presumably linked to xanthine-hypoxanthine altered metabolism. To antagonize the effects of oxyradical pathology, reduced glutathione was administered to a group of patients and the results confirmed the cytoprotective role played by the GSH supplementation. The GSH action was evident on the tissue metabolism and this supports the opinion that reduced glutathione could represent a new and interesting therapeutic approach in marked and acute hypoxic conditions.
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PMID:The role of reduced glutathione during the course of acute haemolysis in glucose-6-phosphate dehydrogenase deficient patients: clinical and pharmacodynamic aspects. 198 80

Glutathione metabolism was studied in isolated hepatocytes from foetal, newborn and adult rats. The GSH/GSSG ratio decreased 15-20-fold through the foetal-neonatal-adult transition. This was mainly due to an increase in GSSG. All enzyme activities involved in the glutathione redox cycle tend to increase during that transition, but the relative increases in glutathione peroxidase and glutathione S-transferase were 3-5 times those of glutathione reductase or glucose-6-phosphate dehydrogenase. GSH synthesis from methionine as a sulphur source was 6 times lower in foetal than in adult hepatocytes. However, when N-acetylcysteine was used as a sulphur donor to by-pass the cystathionine pathway, the rates of GSH synthesis were similar in foetal and adult cells. This is due to the fact that cystathionase activity in foetal cells is very low. This low activity is reflected in the blood amino acid pattern, where the concentration of cysteine rises from 8 to 52 microM from foetuses to adult rats. This supports the idea that cysteine may be an essential amino acid for the premature animal.
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PMID:Physiological changes in glutathione metabolism in foetal and newborn rat liver. 201 16

Lipid peroxide production, antioxidant contents and activities of antioxidative protective enzymes were examined in lungs of rats exposed to clean air (control group), 0.05 ppm O3, 0.05 ppm O3 + 0.04 ppm NO2 and 0.05 ppm O3 + 0.4 ppm NO2 for 22 months. The results were compared with our previous data in rats exposed to 0.04 ppm NO2, 0.4 ppm NO2 and 4 ppm NO2 for their life span (Sagai et al., Toxicol. Appl. Pharmacol., 73, (1984) 444-456). TBA values used as an index of lipid peroxidation in the lungs were increased maximally at 9 months, but were decreased below control values in animals exposed for 18 and 22 months. Nonprotein sulfhydryl (NPSH) contents were increased maximally at 9 months, and after 18 and 22 months were decreased significantly below control values. Vitamin E (VE) contents showed a similar trend. On the other hand, enzyme activities of glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), glutathione reductase (GR), glutathione peroxidase measured by using cumene hydroperoxide (cum.OOH) substrate (GPx-cum.OOH), glutathione peroxidase measured by using H2O2 as a substrate (GPx-H2O2), glutathione S-transferase (GSH-Tase) and superoxide dismutase (SOD) did not show any significant changes during this experiment. The results show that lipid peroxidation in lungs was increased synergistically by a combination of NO2 and O3 at ambient levels, and that the time of maximum lipid peroxide production was shorter than with NO2 alone. The protective ability against lipid peroxides was higher with increased lipid peroxide levels, but the inducibility was not maintained through a life span exposure to the combined gases. Additionally, two small adenomas were observed in 2 out of 18 rats in the 0.05 ppm O3 + 0.04 ppm NO2 group and a large adenoma was observed in 1 out of 18 animals in the 0.05 ppm + 0.4 ppm NO2 group exposed for 22 months.
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PMID:Biochemical effects of combined gases of nitrogen dioxide and ozone. IV. Changes of lipid peroxidation and antioxidative protective systems in rat lungs upon life span exposure. 201 15

To delineate the effect of dietary supplementation with vitamin E (Vit E) alone or in combination with riboflavin (Rib) or selenium (Se) or both, on biological oxidative damage in rat brain and lungs we exposed rats to hyperbaric oxygen (HBO) and measured the activities of glutathione reductase (GSSG-R), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and glucose-6-phosphate dehydrogenase (G-6-PD) prior to or 48 h after exposure. Rats fed the dietary supplements, and a control group maintained on an unsupplemented diet, for 30 d, were each divided into 2 subgroups, of which 1 was exposed to 4.5 absolute atmospheres (ATA) of 100% oxygen for 30 min, hereafter referred to as "exposed". The remaining subgroups were left unexposed. Pre-exposure GSSG-R activity in brain was elevated in all experimentally fed groups (ranging from 23 to 84%) compared with the unexposed control, whereas GSH-Px, G-6-PD and SOD activities were unchanged. The lungs showed significant increases in pre-exposure GSSG-R, ranging from 15 to 28%, and GSH-Px, ranging from 13 to 23%, activities in all the groups fed the supplemental nutrients, except those on Vit E alone. Increases in G-6-PD activity were observed only in those fed supplements of Rib. In most cases exposure to oxygen caused an increase in GSSG-R, GSH-Px and G-6-PD activities. However the increases were higher in the supplemented groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of dietary factors on antioxidant enzymes in rats exposed to hyperbaric oxygen. 203 36


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